1b2i
From Proteopedia
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|PDB= 1b2i |SIZE=350|CAPTION= <scene name='initialview01'>1b2i</scene> | |PDB= 1b2i |SIZE=350|CAPTION= <scene name='initialview01'>1b2i</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=AMH:TRANS-4-AMINOMETHYLCYCLOHEXANE-1-CARBOXYLIC ACID'>AMH</scene> | + | |LIGAND= <scene name='pdbligand=AMH:TRANS-4-AMINOMETHYLCYCLOHEXANE-1-CARBOXYLIC+ACID'>AMH</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Plasmin Plasmin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.7 3.4.21.7] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Plasmin Plasmin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.7 3.4.21.7] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1b2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b2i OCA], [http://www.ebi.ac.uk/pdbsum/1b2i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1b2i RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The kringle 2 (K2) module of human plasminogen (Pgn) binds L-lysine and analogous zwitterionic compounds, such as the antifibronolytic agent trans-(aminomethyl)cyclohexanecarboxylic acid (AMCHA). Far-UV CD and NMR spectra reveal little conformational change in K2 upon ligand binding. However, retarded (1)H-(2)H isotope exchange kinetics induced by AMCHA indicate stabilization of the K2 conformation by the ligand. Assessment of secondary structure content from CD spectra yields approximately 26% beta-STRAND, approximately 13% beta-TURN, approximately 15% 3(1)-HELIX, and approximately 6% 3(10)-HELIX. The NMR solution conformation of the K2 domain complexed to AMCHA has been determined [heavy atom rmsd = 0.49 +/- 0.09A (BACKBONE) AND 1.02+/- 0.08 (ALL)]. The K2 molecule has overall dimensions of approximately 34.5A times approximately 33.4A times approximately 22.7A . Analogous with the polypeptide outline of homologous domains, K2 contains three short antiparallel beta-sheets (paired strands 15-16/20-21, 24-25/48-49, and 62-64/72-74) and four defined beta-turns (residues 6-9, 16-19, 53-56, AND 67-70). Consistent with the CD analysis, albeit novel in the context of kringle folding, the NMR structure reveals an unpaired beta-strand structured by residues 30-32, a turn of 3(10)-helix compromising residues 38-41, and a 3(1)-helix for residues 21-24 and 74-79. We also identify alignable 3(1)-helices in previously reported homologous kringle structures. Rather high order parameter S(2) values (<S(2)>= approximately 0.85 +/- 0.04) characterize the K2 backbone dynamics. The lowest flexibility is observed for the two inner loop segments of residues 51-63 AND 63-75 (<S(2)>= approximately 0.86-0.87 +/- 0.03). Overhauser connectivities reveal close hydrophobic contacts of the ligand ring with side chains of Tyr(36), Trp(62), Phe(64), Trp(72), AND Leu(74). In most K2 structures, the N atom of AMCHA places itself approximately 3.9 and 4.4A from the anionic groups of Glu(57) and Asp(55), respectively, while its carboxylate group, H-bonded to the Tyr(36) side chain OH(eta), ion-pairs the Arg(71) guanidinium group. Consistent with the preference of K2 for binding 5-aminopentanoic acid over 6-aminohexanoic acid, the positions of the ionic centers within the K2 binding site approach each other approximately 1A closer relative to what is observed in lysine binding sites of homologous Pgn modules. | The kringle 2 (K2) module of human plasminogen (Pgn) binds L-lysine and analogous zwitterionic compounds, such as the antifibronolytic agent trans-(aminomethyl)cyclohexanecarboxylic acid (AMCHA). Far-UV CD and NMR spectra reveal little conformational change in K2 upon ligand binding. However, retarded (1)H-(2)H isotope exchange kinetics induced by AMCHA indicate stabilization of the K2 conformation by the ligand. Assessment of secondary structure content from CD spectra yields approximately 26% beta-STRAND, approximately 13% beta-TURN, approximately 15% 3(1)-HELIX, and approximately 6% 3(10)-HELIX. The NMR solution conformation of the K2 domain complexed to AMCHA has been determined [heavy atom rmsd = 0.49 +/- 0.09A (BACKBONE) AND 1.02+/- 0.08 (ALL)]. The K2 molecule has overall dimensions of approximately 34.5A times approximately 33.4A times approximately 22.7A . Analogous with the polypeptide outline of homologous domains, K2 contains three short antiparallel beta-sheets (paired strands 15-16/20-21, 24-25/48-49, and 62-64/72-74) and four defined beta-turns (residues 6-9, 16-19, 53-56, AND 67-70). Consistent with the CD analysis, albeit novel in the context of kringle folding, the NMR structure reveals an unpaired beta-strand structured by residues 30-32, a turn of 3(10)-helix compromising residues 38-41, and a 3(1)-helix for residues 21-24 and 74-79. We also identify alignable 3(1)-helices in previously reported homologous kringle structures. Rather high order parameter S(2) values (<S(2)>= approximately 0.85 +/- 0.04) characterize the K2 backbone dynamics. The lowest flexibility is observed for the two inner loop segments of residues 51-63 AND 63-75 (<S(2)>= approximately 0.86-0.87 +/- 0.03). Overhauser connectivities reveal close hydrophobic contacts of the ligand ring with side chains of Tyr(36), Trp(62), Phe(64), Trp(72), AND Leu(74). In most K2 structures, the N atom of AMCHA places itself approximately 3.9 and 4.4A from the anionic groups of Glu(57) and Asp(55), respectively, while its carboxylate group, H-bonded to the Tyr(36) side chain OH(eta), ion-pairs the Arg(71) guanidinium group. Consistent with the preference of K2 for binding 5-aminopentanoic acid over 6-aminohexanoic acid, the positions of the ionic centers within the K2 binding site approach each other approximately 1A closer relative to what is observed in lysine binding sites of homologous Pgn modules. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Conjunctivitis, ligneous OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173350 173350]], Plasminogen Tochigi disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173350 173350]], Plasminogen deficiency, types I and II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173350 173350]], Thrombophilia, dysplasminogenemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173350 173350]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Marti, D N.]] | [[Category: Marti, D N.]] | ||
[[Category: Schaller, J.]] | [[Category: Schaller, J.]] | ||
| - | [[Category: AMH]] | ||
[[Category: fibrinolysis]] | [[Category: fibrinolysis]] | ||
[[Category: kringle 2]] | [[Category: kringle 2]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:52:20 2008'' |
Revision as of 15:52, 30 March 2008
| |||||||
| Ligands: | |||||||
| Activity: | Plasmin, with EC number 3.4.21.7 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
KRINGLE 2 DOMAIN OF HUMAN PLASMINOGEN: NMR SOLUTION STRUCTURE OF TRANS-4-AMINOMETHYLCYCLOHEXANE-1-CARBOXYLIC ACID (AMCHA) COMPLEX
Overview
The kringle 2 (K2) module of human plasminogen (Pgn) binds L-lysine and analogous zwitterionic compounds, such as the antifibronolytic agent trans-(aminomethyl)cyclohexanecarboxylic acid (AMCHA). Far-UV CD and NMR spectra reveal little conformational change in K2 upon ligand binding. However, retarded (1)H-(2)H isotope exchange kinetics induced by AMCHA indicate stabilization of the K2 conformation by the ligand. Assessment of secondary structure content from CD spectra yields approximately 26% beta-STRAND, approximately 13% beta-TURN, approximately 15% 3(1)-HELIX, and approximately 6% 3(10)-HELIX. The NMR solution conformation of the K2 domain complexed to AMCHA has been determined [heavy atom rmsd = 0.49 +/- 0.09A (BACKBONE) AND 1.02+/- 0.08 (ALL)]. The K2 molecule has overall dimensions of approximately 34.5A times approximately 33.4A times approximately 22.7A . Analogous with the polypeptide outline of homologous domains, K2 contains three short antiparallel beta-sheets (paired strands 15-16/20-21, 24-25/48-49, and 62-64/72-74) and four defined beta-turns (residues 6-9, 16-19, 53-56, AND 67-70). Consistent with the CD analysis, albeit novel in the context of kringle folding, the NMR structure reveals an unpaired beta-strand structured by residues 30-32, a turn of 3(10)-helix compromising residues 38-41, and a 3(1)-helix for residues 21-24 and 74-79. We also identify alignable 3(1)-helices in previously reported homologous kringle structures. Rather high order parameter S(2) values (<S(2)>= approximately 0.85 +/- 0.04) characterize the K2 backbone dynamics. The lowest flexibility is observed for the two inner loop segments of residues 51-63 AND 63-75 (<S(2)>= approximately 0.86-0.87 +/- 0.03). Overhauser connectivities reveal close hydrophobic contacts of the ligand ring with side chains of Tyr(36), Trp(62), Phe(64), Trp(72), AND Leu(74). In most K2 structures, the N atom of AMCHA places itself approximately 3.9 and 4.4A from the anionic groups of Glu(57) and Asp(55), respectively, while its carboxylate group, H-bonded to the Tyr(36) side chain OH(eta), ion-pairs the Arg(71) guanidinium group. Consistent with the preference of K2 for binding 5-aminopentanoic acid over 6-aminohexanoic acid, the positions of the ionic centers within the K2 binding site approach each other approximately 1A closer relative to what is observed in lysine binding sites of homologous Pgn modules.
About this Structure
1B2I is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure and dynamics of the plasminogen kringle 2-AMCHA complex: 3(1)-helix in homologous domains., Marti DN, Schaller J, Llinas M, Biochemistry. 1999 Nov 30;38(48):15741-55. PMID:10625440
Page seeded by OCA on Sun Mar 30 18:52:20 2008
